TIGIT and PD-1 Mark Intratumoral T Cells with Reduced Effector Function in B-cell Non-Hodgkin Lymphoma

Cancer Immunol Res. 2019 Mar;7(3):355-362. doi: 10.1158/2326-6066.CIR-18-0351. Epub 2019 Jan 18.


Checkpoint blockade can reverse T-cell exhaustion and promote antitumor responses. Although blocking the PD-1 pathway has been successful in Hodgkin lymphoma, response rates have been modest in B-cell non-Hodgkin lymphoma (NHL). Coblockade of checkpoint receptors may therefore be necessary to optimize antitumor T-cell responses. Here, characterization of coinhibitory receptor expression in intratumoral T cells from different NHL types identified TIGIT and PD-1 as frequently expressed coinhibitory receptors. Tumors from NHL patients were enriched in CD8+ and CD4+ T effector memory cells that displayed high coexpression of TIGIT and PD-1, and coexpression of these checkpoint receptors identified T cells with reduced production of IFNγ, TNFα, and IL2. The suppressed cytokine production could be improved upon in vitro culture in the absence of ligands. Whereas PD-L1 was expressed by macrophages, the TIGIT ligands CD155 and CD112 were expressed by lymphoma cells in 39% and 50% of DLBCL cases and in some mantle cell lymphoma cases, as well as by endothelium and follicular dendritic cells in all NHLs investigated. Collectively, our results show that TIGIT and PD-1 mark dysfunctional T cells and suggest that TIGIT and PD-1 coblockade should be further explored to elicit potent antitumor responses in patients with NHL.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Cell Line, Tumor
  • Cytokines / metabolism
  • Female
  • Humans
  • Immunologic Memory
  • Ligands
  • Lymphoma, Non-Hodgkin / metabolism
  • Lymphoma, Non-Hodgkin / pathology*
  • Middle Aged
  • Programmed Cell Death 1 Receptor / metabolism*
  • Receptors, Immunologic / metabolism*
  • T-Lymphocyte Subsets / metabolism*
  • Tumor Microenvironment


  • Cytokines
  • Ligands
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • Receptors, Immunologic
  • TIGIT protein, human